Inheritance Analysis of Bolting Associated Traits Using Mixed Major Gene Plus Polygene Model in Brassica rapa

[ Objective ] This study aimed to analyze the inheritance of bolting associated traits in Brassica rapa, which will provide useful information in a breeding program for late-bolting or bolting-resistant cultivars of Chinese cabbage. [ Method] Three phenotypic measurements, bolting index, flowering time, days to 5 cm elongated stalk, respectively were used for inheritance analysis of six generations, P, （bolting resistant inbreed line ）, P2 （vernalization independent type） and their filial generations F1 , B1, B2 and F2, using the mixed major-gene plus polygene inheritance model. [ Result] The two traits, bolting index and days to 5 cm elongated stalk, both were controlled by two major genes with additive-dominant-epistatic effects （ B-1 model） in hybrid. The flowering time was controlled by one major gene with addltive-dominant effects plus additive-dominant-epistatic effects （D model）. The heritability of the major genes in B1, B2 and F2 were 96.22%, 93.33%, 93.55% for bolting index, 70.68%, 70.68%, 70.64% for flowering time, 79.44%, 79.55%, 79.38% for days to 5-cm elongated stalk, respectively, but no polygene heritability was detected in BI, B2 and F2 generation. It indicated that the bolting trait in Brassica rapa was controlled by one or tow major genes. [ Conclusion] This implied that in the genetic improvement for bolting resistant trait major gene was a main factor. It is fit for early selection and environment factor should be mentioned.

Genetic Analysis of Stripe Disease Resistance in Rice Restorer Line C224 Using Major Gene plus Polygene Mixed Effect Model

The inheritance of stripe disease resistance in a rice restorer line C224 was analyzed using the mixed effect model of major gene plus polygene for quantitative traits.In addition,the resistance was investigated in seven crosses of C224 with maintainer lines.The results showed that the stripe resistance of C224 was controlled by two major genes with additive-dominance-epistasis effects plus polygenes with additive-dominance effects （E-1 model）.These two genes had additive effects of-12.47% and-24.75%,respectively,showing negative dominance effects.There were significant epistasis and interaction effects between the two major genes.The heritability of the two major genes was 92.12%,while that of polygenes was 2.74%,indicating that the stripe resistance had dominant major gene effect.Of the seven crosses,five displayed high or medium resistance to the stripe disease.

Animal models of genetic causes of male infertility

Introduction In the past 10 years, more than 100 different genetically engineered mice have been developed with an abnormality in spermatogenesis. More than half of these male infertility animal models have been reported in the past three years alone. Spermatogenic defects in these models vary considerably, ranging from the inappropriate migration of primordial germ cells to the inability of mature spermatozoa to bind the zona pellucida. Many of

Expression Pattern of Testis-specific Expressed Gene 2 in Cryptorchidism Model and Its Role in Apoptosis of Spermatogenic Cells

In our previous study, we identified a novel testis-specific expressed gene 2 （TSEG-2） from mouse testis. To further investigate its functions, 35 male Balb/c mice （8 weeks old） were divided into cryptorchidism group （n=20）, sham group （n=10）, and control group （n=5）. In cryptorchidism group, the right testes were anchored to the inner lateral abdominal wall. In situ hybridization （ISH） was applied to measure the localization of TSEG-2 in mouse testis. Real-time quantitative PCR was performed to detect the expression of TSEG-2 gene. Meanwhile, under the mediation of polyethylenimine （PEI）, the recombinant vector pEGFP-TSEG-2 （n=5） or empty vector （mock, n=5） was transfected into the testis of male mice. The transfection efficiencies were measured under a fluorescence microscope. The apoptosis of spermatogenic cells was detected by terminal deoxynuleotidyl-mediated nick end labeling （TUNEL）. The results showed that TSEG-2 was expressed in convoluted seminiferous tubules, more precisely, in spermatogonia and spermatocytes. As compared with sham and control groups, the TSEG-2 transcription was significantly enhanced （P〈0.05） and was correlated with apoptosis of spermatogenic cells in cryptorchid testes （P〈0.05）. PEI was efficient in mediating transfeetion of TSEG-2 into seminiferous tubules of testis. One week post-transfection, intratesticular injection of TSEG-2 resulted in increased apoptosis of spermatogenic cells in vivo （P〈0.05）. These results indicate that TSEG-2 may participate in the apoptosis of spermatogenic cells and the pathogenesis of cryptorchidism.

Mouse models for the discovery of colorectal cancer drivergenes

Colorectal cancer(CRC) constitutes a major publichealth problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations(e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC.

A 3-D in vitro tumor model for investigation of bacteria-mediated gene delivery

Introduction Cancer is an attractive target of gene therapy and currently represents the disease in most clinical trials[1]. Strategies for cancer gene therapy include: (1) stimulation of immune responses to tumor cells,(2) delivery of specific enzymes

High yield reproducible rat model recapitulating human Barrett's carcinogenesis

AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression stages.RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.

Hepatocellular carcinoma mouse models:Hepatitis B virusassociatedhepatocarcinogenesis and haploinsufficienttumor suppressor genes

The multifactorial and multistage pathogenesis of hepatocellular carcinoma(HCC)has fascinated a wide spectrum of scientists for decades.While a number of major risk factors have been identified,their mechanistic roles in hepatocarcinogenesis still need to be elucidated.Many tumor suppressor genes(TSGs)have been identified as being involved in HCC.These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors:the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele.Hepatitis B virus(HBV)is one of the most important risk factors associated with HCC.Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor,one advantage of mouse models for HBV/HCC research is the numerous and powerfulgenetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs.Here,we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner.Discoveries obtained using mouse models will have a great impact on HCC translational medicine.

The application of hidden markov model in building genetic regulatory network

The research hotspot in post-genomic era is from sequence to function. Building genetic regulatory network (GRN) can help to understand the regulatory mechanism between genes and the function of organisms. Probabilistic GRN has been paid more attention recently. This paper discusses the Hidden Markov Model (HMM) approach served as a tool to build GRN. Different genes with similar expression levels are considered as different states during training HMM. The probable regulatory genes of target genes can be found out through the resulting states transition matrix and the determinate regulatory functions can be predicted using nonlinear regression algorithm. The experiments on artificial and real-life datasets show the effectiveness of HMM in building GRN.

Effect of warm acupuncture on nitric oxide synthase and calcitonin gene-related peptide in a rat model of lumbar nerve root compression

BACKGROUND： Varying degrees of inflammatory responses occur during lumbar nerve root compression. Studies have shown that nitric oxide synthase （NOS） and calcitonin gene-related peptide （CGRP） are involved in secondary disc inflammation. OBJECTIVE： To observe the effects of warm acupuncture on the ultrastructure of inflammatory mediators in a rat model of lumbar nerve root compression, including NOS and CGRP contents. DESIGN, TIME AND SETTING： Randomized, controlled study, with molecular biological analysis, was performed at the Experimental Center, Sixth People＇s Hospital Affiliated to Shanghai Jiao Tong University, between September 2006 and April 2007. MATERIALS： Acupuncture needles and refined Moxa grains were purchased from Shanghai Taicheng Technology Development Co., Ltd., China; Mobic tablets were purchased from Shanghai Boehringer Ingelheim Pharmaceuticals Co., Ltd., China; enzyme linked immunosorbent assay （ELISA） kits for NOS and CGRP were purchased from ADL Biotechnology, Inc., USA. METHODS： A total of 50, healthy, adult Sprague-Dawley rats, were randomly divided into five groups normal, model, warm acupuncture, acupuncture, and drug, with 10 rats in each group. Rats in the four groups, excluding the normal group, were used to establish models of lumbar nerve root compression. After 3 days, Jiaji points were set using reinforcing-reducing manipulation in the warm acupuncture group. Moxa grains were burned on each needle, with 2 grains each daily. The acupuncture group was the same as the warm acupuncture group, with the exception of non-moxibustion. Mobic suspension （3.75 mg/kg） was used in the oral drug group, once a day. Treatment of each group lasted for 14 consecutive days. Modeling and medication were not performed in the normal group. MAIN OUTCOME MEASURES： The ultrastructure of damaged nerve roots was observed with transmission electron microscopy; NOS and CGRP contents were measured using ELISA. RESULTS： The changes of the radicular ultramicrostructure were characterized by Wallerian degeneration; nerve fibers were clearly demyelinated; axons collapsed or degenerated; outer Schwann cell cytoplasm was swollen and its nucleus was compacted. Compared with the normal group, NOS and CGRP contents in the nerve root compression zone in the model group were significantly increased （P 〈 0.01）. Nerve root edema was improved in the drug, acupuncture and the warm acupuncture groups over the model group. NOS and CGRP expressions were also decreased with the warm acupuncture group having the lowest concentration （P 〈 0.01）. CONCLUSION： In comparison to the known effects of Mobic drug and acupuncture treatments, the warm acupuncture significantly decreased NOS and CGRP expression which helped improve the ultrastructure of the compressed nerve root.

A Qualitative Model of the Interaction of Sexual Behavior and Hormone Gene Transcription in Male Blue Gourami during Reproduction

In the present study, a model is suggested to describe hormone control in male blue gourami (Trichogaster trichopterus) along the gonadotropic brain-pituitary- gonad axis (BPG axis) and the hypothalamic-pituitary-somatotropic axis (HPS axis). This model is based on the cloning and transcription of genes encoding hormones of the two axes involved in spermatogenesis during blue gourami reproduction. Gene transcription is affected by environmental, biological, and behavioral factors. Mature males were examined in two different stages—nonreproductive in high-density habitats and reproductive in low-density habitats. Based on gene transcription, gonadotropin-releasing hormone 1 (GnRH1) was involved in controlling spermatogenesis (spermatogonia to spermatids) via the BPG axis in nonreproductive and reproductive stages by controlling follicle-stimulating hormone (FSH), 11-ketotestosterone (11KT) and 17β-estradiol (E2). However, GnRH3 had a larger effect during the reproductive stage via the BPG axis (spermatids to sperm) on luteinizing hormone (LH), 11KT, and 17α-hydroxyprogesterone (17P). At the same time, the HPS axis was involved in spermatogenesis via pituitary adenylate cyclase-activating polypeptide (PACAP) and its related peptide PRP (formerly known as GHRH-like peptide) in the brain, and growth hormone (GH) in the pituitary affected synthesis of insulin-like growth factor 1 (IGF1) in the liver.

Gene environment interaction in periphery and brain converge to modulate behavioral outcomes:Insights from the SP1 transient early in life interference rat model

It is generally assumed that behavior results from an interaction between susceptible genes and environmental stimuli during critical life stages.The present article reviews the main theoretical and practical concepts in the research of gene environment interaction,emphasizing the need for models simulating real life complexity.We review a novel approach to study gene environment interaction in which a brief post-natal interference with the expression of multiple genes,by hindering the activity of the ubiquitous transcription factor specificity protein 1(Sp1) is followed by later-in-life exposure of rats to stress.Finally,this review discusses the role of peripheral processes in behavioral responses,with the Sp1 model as one example demonstrating how specific behavioral patterns are linked to modulations in both peripheral and central physiological processes.We suggest that models,which take into account the tripartite reciprocal interaction between the central nervous system,peripheral systems and environmental stimuli will advance our understanding of the complexity of behavior.

Rapid Prototype Development Approach for Genetic Programming

Genetic Programming (GP) is an important approach to deal with complex problem analysis and modeling, and has been applied in a wide range of areas. The development of GP involves various aspects, including design of genetic operators, evolutionary controls and implementations of heuristic strategy, evaluations and other mechanisms. When designing genetic operators, it is necessary to consider the possible limitations of encoding methods of individuals. And when selecting evolutionary control strategies, it is also necessary to balance search efficiency and diversity based on representation characteristics as well as the problem itself. More importantly, all of these matters, among others, have to be implemented through tedious coding work. Therefore, GP development is both complex and time-consuming. To overcome some of these difficulties that hinder the enhancement of GP development efficiency, we explore the feasibility of mutual assistance among GP variants, and then propose a rapid GP prototyping development method based on πGrammatical Evolution (πGE). It is demonstrated through regression analysis experiments that not only is this method beneficial for the GP developers to get rid of some tedious implementations, but also enables them to concentrate on the essence of the referred problem, such as individual representation, decoding means and evaluation. Additionally, it provides new insights into the roles of individual delineations in phenotypes and semantic research of individuals.

加权共表达网络分析与机器学习识别类风湿关节炎滑膜中的关键基因

背景:类风湿关节炎是一种全身的免疫相关性疾病,主要病理特点是关节滑膜炎性增生及关节软骨的破坏,其发病机制目前尚不明确,迫切需要发现新的具有高度敏感性和特异性的诊断标志物。目的:联合使用生物信息学技术及计算机学习算法,识别并筛选类风湿关节炎患者滑膜中的关键基因,构建类风湿关节炎预测模型并进行验证。方法:从基因表达综合数据库中下载3个包含类风湿关节炎患者滑膜的数据集(GSE77298、GSE55235、GSE55457),GSE77298和GSE55235作为训练集,GSE55457作为测试集,共纳入66个样本,其中类风湿关节炎患者滑膜样本39个,正常滑膜样本27个。应用R语言筛选训练集中的差异基因,然后使用加权共表达网络将训练集中的基因模块化,选出关键模块中的特征基因,将差异表达基因和特征基因取交集,交集基因进入下一步机器学习。采用3种机器学习方法:最小绝对值收敛和选择算子算法、支持向量机-递归特征消除和随机森林算法对交集基因进一步分析获得枢纽基因,将枢纽基因再次相交即得到类风湿关节炎滑膜中的关键基因。以关键基因为变量构建预测类风湿关节炎的列线图模型,推测患者发生类风湿关节炎的危险程度,使用受试者工作特征曲线确定类风湿关节炎预测模型及其关键基因的诊断价值。结果与结论:①通过差异分析,训练集中共筛选出差异基因730个,加权共表达网络分析得到特征基因185个,两者交集基因159个;②最小绝对值收敛和选择算子发现枢纽基因4个,支持向量机-递归特征消除发现枢纽基因11个,随机森林发现枢纽基因5个,取交集后获得关键基因2个(TNS3、SDC1);③基于2个关键基因,在训练集及测试集种构建列线图,其校准预测曲线与标准曲线贴合较好,且预测类风湿关节炎发生的临床效能良好;④上述结果证实,基于生物信息及机器学习算法获得的TNS3和SDC1有可能成为类风湿关节炎诊断和治疗的关键靶点。

HumGene:一个基于GHMM的人类基因预测软件

HumGene是一个采用广义隐Markov模型(GHMM)的人类基因预测软件.利用人类基因的结构特点,采用概率模型为基因结构中各个特定区域建立了独立的子模型,能够获得全局统一的评价指数,使得系统整体框架具有一定的扩展性.采用一种新的简化算法,有效地降低了计算的复杂度.介绍了软件的构成,对软件进行了测试,给出了与其它类似软件的结果比较.

Genetic Analysis of Embryo Production Frequency in Wheat × Maize Cross

A DH population derived from C49S-87/01Y1-1069 was used to study the inheritance of wheat haploid embryo production frequency（EPF） in wheat × maize cross with the mixed major gene and polygene inheritance model of quantitative traits. The results showed that the EPF of wheat × maize cross was controlled by two dominant epistatic genes and polygene with gene effects of 1.95 for the first major gene, 6.69 for the second one and 2.80 for the polygene. The inheritability of major genes was as high as 72.09%, suggesting that the differences in EPF among wheat materials were mainly influenced by genotype. However, non-genetic factors were still important, especially for wheat materials with low EPF.

Genetic Analysis on Plant Height in Rice in Different Growing Seasons

[Objective] The aim was to carry out the genetic analysis on plant height of rice（Oryza sativa L.）cultivated in different seasons.[Method] Three rice parents with great difference in plant height including CB1（83.1 cm）,CB4（105.5 cm）and CB7（115.6 cm）were chosen to construct two parental combinations：CB1×CB4 and CB7×CB4,and the corresponding filial generations P1,F1,P2,B1,B2 and F2 were obtained.The 6 populations were planted in middle and late seasons respectively to measure their height traits.The Akaike＇s information criterion（AIC）of the mixed major gene and polygene model was used to indentify the existence of major genes affecting quantitative traits in B1,B2,F2 populations.When the major genes existed,the genetic effects of the major genes and polygenes and their genetic variance were estimated through segregation analysis.[Result] One additive major gene plus additive-dominance polygenes was the most fitted genetic model for the trait in all B1,B2,F2 populations in two planting seasons.The heritability values of the major genes varied from 38.63% to 78.53% and those of polygenes varied from 1.72% to 36.04%,and the total heritability values were 45.52-92.93%.The additive effect d value of the two genetic populations under two planting seasons was-4.56,-9.16,-7.19,and-9.38,respectively,as suggested that additive effect of the major genes would decrease the express of the plant height trait.[Conclusion] The heritability of plant height trait was affected by planting seasons and the combinations clearly as a whole.

两种肌少症小鼠模型的功能表型、肌肉质量及力量特点比较

背景:地塞米松和后肢悬吊是常用的动物肌少症造模方法,具有造模时间短、操作简便、成本低等特点。目的:比较地塞米松和后肢悬吊诱导小鼠肌少症模型在肌肉质量、力量及功能表型以及分子机制表型方面的差异。方法:采用随机抽样法将30只C57BL/6小鼠随机分成3组,每组10只:正常对照组不进行任何干预;地塞米松组小鼠腹腔注射地塞米松磷酸钠溶液1 mg/(kg•d),连续注射6周,建立肌少症模型;后肢悬吊组采用鼠尾套悬吊小鼠后肢16 h,1次/d,连续悬吊6周,建立肌少症模型。造模6周内,监测小鼠体质量变化;造模6周后,检测小鼠四肢抓力、活动能力(游泳实验)、骨骼肌湿质量、骨骼肌病理形态,采用RT-PCR与Western blot检测骨骼肌蛋白质合成与分解代谢指标、AMPK/FoXO3α信号通路的表达。结果与结论:①从造模后第2周开始,地塞米松组、后肢悬吊组小鼠体质量均低于正常对照组(P<0.05)。②造模6周后,与正常对照组相比,造模两组小鼠四肢抓力均下降(P<0.05),腓肠肌湿质量、趾长伸肌湿质量、腓肠肌与比目鱼肌横截面积均下降(P<0.05);地塞米松组小鼠腓肠肌横截面积明显小于后肢悬吊组(P<0.05),比目鱼肌横截面积大于后肢悬吊组(P<0.05);与正常对照组、后肢悬吊组相比,地塞米松组小鼠活动能力降低(P<0.05)。③与正常对照组相比,造模两组PI3K、mTOR、AMPK、PGC-1αmRNA表达与p-AMPK/AMPK蛋白均降低(P<0.05),FoXO3αmRNA表达与PGC-1α、FoXO3蛋白表达均升高(P<0.05);地塞米松组Akt1 mRNA表达降低(P<0.05),Atrogin-1、MuRF-1 mRNA表达升高(P<0.05);后肢悬吊组Akt1 mRNA表达升高(P<0.05)。④与地塞米松组相比,后肢悬吊组mTOR、Akt1、FoXO3αmRNA表达升高(P<0.05),Atrogin-1、MuRF-1 mRNA表达降低(P<0.05)。⑤结果表明,两种造模方法均会导致骨骼肌线粒体能量代谢水平下降,地塞米松组通过泛素蛋白酶体和能量代谢途径的双重作用介导骨骼肌发生萎缩,后肢悬吊组通过AMPK/FoXO3α信号通路介导能量代谢途径引起骨骼肌发生萎缩,从而引起骨骼肌的质量、力量及功能下降。

Creating animal models, why not use the Chinese tree shrew ( Tupaia belangeri chinensis)？

The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew （Tupaia belangeri） aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database （www.treeshrewdb.org） has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 （HSV-1） and hepatitis C virus （HCV） infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.

Genetic Effects of H-FABP Gene on Some Pig Economic Important Traits in a F2 Resource Population

The F2 design was used in construction of the pig resource population, and 14 economic important traits of 119 F2 offspring were measured. The polymorphisms of heart fatty acid binding protein gene (H-FABP) were detected by PCR-RFLP. The effects of different H-FABP genotypes were analyzed by a fixed model. The results showed that, the carcass composition traits were affected by H-FABP gene significantly, backfat thickness alive, carcass backfat thickness between 6th - 7th rib, and average carcass backfat thickness, of different H-FABP genotypes were significantly different (P<0. 05). The dominant effects on the traits demonstrated that the gene affected the carcass composition traits overdominantly. The results also showed that H-FABP gene affected the growth traits and meat quality traits, and the pH, of different H-FABP genotypes was significantly different.